A Novel Missense Mutation in a Compound Heterozygous Patient with Fish-Eye Disease: A Case Report.

INTRODUCTION

Fish-eye disease (FED) is a rare autosomal recessive disorder caused by a partial deficiency of lecithin-cholesterol acyltransferase (LCAT) activity. It is characterized by progressive corneal opacification and dyslipidemia in the absence of systemic manifestations. We describe the clinical presentation, optical coherence tomography (OCT) imaging findings, and Scheimpflug-based corneal densitometry results in a patient with FED carrying both a pathogenic variant and a novel missense variant of the LCAT gene not reported in the current literature.

CASE PRESENTATION: We present a rare case of a 25-year-old female with bilateral corneal opacities, reduced plasma high-density lipoprotein cholesterol (<5 mg/dL), and elevated low-density lipoprotein cholesterol levels (>133 mg/dL). Visual acuity remained 20/20 in both eyes. Slit-lamp examination revealed diffuse subepithelial and anterior stromal deposits. The central corneal thickness was thinner than normal on Scheimpflug tomography, measuring 419 µm OD and 409 µm OS. OCT findings confirmed stromal thinning (479 µm OD and 470 µm OS), with preserved central epithelial thickness, and demonstrated corneal opacities throughout the cornea. Mean densitometry across the 12-mm corneal diameter was more than double that reported in healthy corneas. The cholesteryl ester-to-total cholesterol ratio remained within the normal range. Genetic analysis identified a previously reported pathogenic variant in exon 4 of LCAT (c.440C>T, p.Thr147Ile) and a novel missense mutation in exon 5 (c.715G>A, p.Gly239Ser), classified as a variant of uncertain significance.

CONCLUSION

FED is a rare genetic disorder that is associated with corneal clouding and dyslipidemia. Genetic analysis confirmed the diagnosis with a compound heterozygous genotype, while OCT and corneal densitometry were effective modalities for quantifying and characterizing lipid deposits in FED.